2017-09-24 11:46:50

Today's Topics

  • Neurochemistry
    • How neurons talk to one another
  • Synaptic communication
  • Neurotransmitters

In the beginning

  • Soma receives input from dendrites
  • Axon hillock sums/integrates
  • If sum > threshold, AP "fires"

Illustration of summation

Steps in synaptic transmission

  • Rapid change in voltage triggers neurotransmitter (NT) release
  • Voltage-gated calcium Ca++ channels open
  • Ca++ causes synaptic vesicles to bind with presynaptic membrane, merge, exocytosis

Steps in synaptic transmission

  • NTs diffuse across synaptic cleft
  • NTs bind with receptors on postsynaptic membrane
  • Receptors respond
  • NTs unbind, are inactivated

Synaptic transmission

Excocytosis

Why do NTs move from presynaptic terminal toward postsynaptic cell?

  • Electrostatic force pulls them
  • Force of diffusion

Why do NTs move from presynaptic terminal toward postsynaptic cell?

  • Electrostatic force pulls them
  • Force of diffusion

Postsynaptic receptor types

Postsynaptic receptor types

  • Ligand-gated ion channels
  • Ionotropic (receptor + ion channel)
    • Ligand-gated
    • Open/close channel
    • Faster, but short-acting effects

Postsynaptic receptor types

  • Metabotropic (receptor only)
    • Trigger 2nd messengers
    • G-proteins
    • Open/close adjacent channels, change metabolism
    • Slower, but longer lasting effects

Receptor types

Receptors generate postsynaptic potentials (PSPs)

  • Small voltage changes
  • Amplitude scales with # of receptors activated
    • Dendrites usually lack voltage gated Na+ channels
  • Excitatory PSPs (EPSPs)
    • Depolarize neuron (make more +)
  • Inhibitory (IPSPs)
    • Hyperpolarize neuron (make more -)

NTs inactivated

  • Buffering
  • Reuptake via transporters
    • molecules in membrane that move NTs inside
    • e.g., serotonin via serotonin transporter (SERT)
  • Enzymatic degradation
    • e.g., acetylcholinesterase (AChE) degrades acetylcholine (ACh)

Questions to ponder

  • Why must NTs be inactivated?

Questions to ponder

  • Why must NTs be inactivated?
    • Keeps messages discrete, localized in time and space
    • Maximizes concentration gradient

What sort of PSP would opening a Na+ channel produce?

  • Excitatory PSP, Na+ flows in
  • Excitatory PSP, Na+ flows out
  • Inhibitory PSP, Na+ flows in
  • Inhibitory PSP, Na+ flows out

What sort of PSP would opening a Na+ channel produce?

  • Excitatory PSP, Na+ flows in
  • Excitatory PSP, Na+ flows out
  • Inhibitory PSP, Na+ flows in
  • Inhibitory PSP, Na+ flows out

What sort of PSP would opening a Cl- channel produce?

Remember [Cl-out]>>[Cl-in]

  • Excitatory PSP, Cl- flows in
  • Excitatory PSP, Cl- flows out
  • Inhibitory PSP, Cl- flows in
  • Inhibitory PSP, Cl- flows out

What sort of PSP would opening a Cl- channel produce?

Remember [Cl-out]>>[Cl-in]

  • Excitatory PSP, Cl- flows in
  • Excitatory PSP, Cl- flows out
  • Inhibitory PSP, Cl- flows in
  • Inhibitory PSP, Cl- flows out

Types of synapses

Synapses on

  • dendrites
    • usually excitatory
  • cell bodies
    • usually inhibitory
  • axons
    • usually modulatory (change p(fire))

Summary of chemical transmission

Neurotransmiters

Glutamate

  • Primary excitatory NT in CNS
  • Role in learning (via NMDA)
  • Receptors on neurons and glia (astrocytes and oligodendrocytes)
  • Linked to umami (savory) taste sensation, think MSG
  • Dysregulation in schizophrenia? (Javitt 2010)

Glutamate

Type Receptor Esp Permeable to
Ionotropic AMPA Na+, K+
Kainate
NMDA Ca+
Metabotropic mGlu

\(\gamma\) aminobutyric acid (GABA)

  • Primary inhibitory NT in CNS
  • Excitatory in developing CNS, [Cl-] in >> [Cl-] out
  • Binding sites for benzodiazepines (e.g., Valium), barbiturates, ethanol, etc.
Type Receptor Esp Permeable to
Ionotropic GABA-A Cl-
Metabotropic GABA-B K+

GABA

Other amino acid NTs

  • Aspartate
    • Like Glu, stimulates NMDA receptor
  • Glycine
    • Spinal cord interneurons

Acetylcholine (ACh)

  • Primary excitatory NT of CNS output
  • Somatic nervous system (motor neuron -> neuromuscular junction)
  • Autonomic nervous system
    • Sympathetic branch: preganglionic neuron
    • Parasympathetic branch: pre/postganglionic

ACh anatomy

Acetylcholine

Type Receptor Esp Permeable to Blocked by
Ionotropic Nicotinic (nAChR) Na+, K+ e.g., Curare
Metabotropic Muscarinic (mAChR) K+ e.g., Atropine

Curare

Atropine

References

Anderson, Christopher M., and Raymond A. Swanson. 2000. “Astrocyte Glutamate Transport: Review of Properties, Regulation, and Physiological Functions.” Glia 32 (1). John Wiley & Sons, Inc.: 1–14. doi:10.1002/1098-1136(200010)32:1<1::AID-GLIA10>3.0.CO;2-W.

Javitt, Daniel C. 2010. “Glutamatergic Theories of Schizophrenia.” Israel Journal of Psychiatry and Related Sciences 47 (1): 4.